T-cell acute lymphoblastic leukemia (T-ALL) is a highly aggressive hematologic malignancy with a poor prognosis, despite advancements in treatment. Many patients struggle with relapse or refractory disease. Investigating the role of the super-enhancer (SE) regulated gene ubiquitin-specific protease 20 (USP20) in T-ALL could enhance targeted therapies and improve clinical outcomes. Analysis of histone H3 lysine 27 acetylation (H3K27ac) chromatin immunoprecipitation sequencing (ChIP-seq) data from six T-ALL cell lines and seven pediatric samples identified USP20 as an SE-regulated driver gene. Utilizing the Cancer Cell Line Encyclopedia (CCLE) and BloodSpot databases, it was found that USP20 is specifically highly expressed in T-ALL. Knocking down USP20 with short hairpin RNA (shRNA) increased apoptosis and inhibited proliferation in T-ALL cells. In vivo studies showed that USP20 knockdown reduced tumor growth and improved survival. The USP20 inhibitor GSK2643943A demonstrated similar anti-tumor effects. Mass spectrometry, RNA-Seq, and immunoprecipitation revealed that USP20 interacted with hypoxia-inducible factor 1 subunit alpha (HIF1A) and stabilized it by deubiquitination. Cleavage under targets and tagmentation (CUT&Tag) results indicated that USP20 co-localized with HIF1A, jointly modulating target genes in T-ALL. This study identifies USP20 as a therapeutic target in T-ALL and suggests GSK2643943A as a potential treatment strategy.

Objective:To explore the alterations in functional connectivity density (FCD) resulted from mild cognitive impairment (MCI) and their correlations with cognitive scores in various cognitive domains in patients with Parkinson's disease (PD).Methods:Forty-three PD patients admitted to Department of Neurology, Sixth Affiliated Hospital of Nantong University from January 2022 to April 2024 were selected and divided into PD-MCI group (MoCA scores<26) and PD with normal cognition (PD-NC) group (MoCA scores≥26) according to Montreal Cognitive Assessment (MoCA). Another 23 middle-aged and elderly healthy volunteers (HC group) matched with PD patients in age, gender and education level were recruited at the same period. Resting-state functional MRI (rs-fMRI) data were collected and whole brain FCD was calculated. Differences of clinical data, whole brain FCD, and FCD in brain regions with significantly different FCD among the 3 groups were compared. Efficiency of FCD in brain regions with significantly different FCD between PD-MCI group and PD-NC group in differentially diagnosing PD-MCI and PD-NC was analyzed by receiver operating characteristic (ROC) curve. Pearson correlation was used to the analyze the correlations of FCD in brain regions with significantly different FCD with MoCA score and cognitive scores in various cognitive domains.Results:Among the 43 patients, 23 were into the PD-MCI group and 20 into the PD-NC group. PD-MCI group had significantly lower scores in the visuospatial and executive function, abstraction, and delayed memory cognitive domains than PD-NC group ( P<0.05). Brain regions with significantly different FCD among the 3 groups were the right parahippocampal gyrus, left gyrus rectus, right rolandic operculum, left middle occipital gyrus, right precentral gyrus, left middle frontal gyrus, and left medial superior frontal gyrus. Compared with the HC group, the PD-MCI group and PD-NC group had significantly increased FCD at the right parahippocampal gyrus, left gyrus rectus and right rolandic operculum, statistically decreased FCD at the right precentral gyrus, left middle frontal gyrus, and left medial superior frontal gyrus ( P<0.05). Compared with the HC group, the PD-MCI group had significantly increased FCD at the left middle occipital gyrus ( P<0.05). Compared with the PD-NC group, the PD-MCI group had significantly decreased FCD at the right parahippocampal gyrus, and statistically increased FCD at the left middle occipital gyrus and left middle frontal gyrus ( P<0.05). Area under ROC curve (AUC) of FCD in brain regions with significantly different FCD in discriminating PD-MCI and PD-NC was 0.878, with sensitivity of 90.0% and specificity of 91.3%. FCD at right parahippocampal gyrus, left middle occipital gyrus and left middle frontal gyrus was negatively correlated with MoCA score ( P<0.05); FCD at right parahippocampal gyrus was positively correlated with cognitive scores in the visuospatial and executive function, and delayed memory domains ( P<0.05); FCD at left middle occipital gyrus was negatively correlated with cognitive scores in the executive function and visual-spatial skills, and abstraction domains ( P<0.05); FCD at the left medial frontal gyrus was negatively correlated with cognitive scores in the visuospatial and executive function, abstraction and delayed memory domains ( P<0.05). Conclusions:Abnormal FCD can be noted in some brain regions of PD patients, enjoying differences between PD-MCI patients and PD-NC patients. Combined FCD in brain regions with significantly different FCD has high value in differentially diagnosing PD-MCI and PD-NC, and FCD in brain regions with significantly different FCD is correlated with cognitive function changes in PD patients.

Objective To explore the clinical effect and nursing cooperation of the new robot-assisted puncture system RC120 in CT-guided lung puncture biopsy,so as to provide practical basis for the promotion and utilization of the new robot-assisted puncture system.Methods Using random sampling method,a total of 29 patients,who received robot-assisted lung puncture at the Shanghai Municipal Pulmonary Hospital of China between January and June of 2022,were collected as the study group,while other 29 patients,who received traditional manual lung puncture under CT guidance in the same period,were collected as the control group.For the patients of the control group traditional nursing was implemented,while for the patients of the study group on the basis of traditional nursing the additional targeted nursing care was carried out.The accuracy of puncture localization,satisfaction with the nursing care,and incidence of complications were compared between the two groups.Results The accuracy of puncture localization in the study group was 5.0 mm(3.6-6.2 mum),which was better than 6.4 mm(4.0-8.4 mm)in the control group,and the difference was statistically significant(Z=-2.179,P=0.034).The patient satisfaction score in the study group was(91.1±1.6)points,which was significantly higher than(82.2±1.7)points in control group,and the difference was statistically significant(t=21.047,P＜0.001).In the study group 2 patients developed complications with an incidence of 6.9％,while in the control group 8 patients developed complications with an incidence of 27.6％,and the difference was statistically significant(x2=4.350,P=0.037).Conclusion The implementation of targeted nursing care can reduce the risk of complications caused by CT-guided lung puncture with RC120 auxiliary puncture system,improve the accuracy of puncture localization,and improve patient satisfaction with nursing care,therefore,the targeted nursing care deserves promotion in clinical practice.(J Intervent Radiol,2024,33:549-553)

Post-stroke depression (PSD) is an important mental complication of stroke, affecting nearly 1/3 of stroke patients, seriously affecting patients' functional recovery and quality of life, and is associated with increased mortality of stroke patients. Traditional antidepressant treatments include medication and psychotherapy, but there may be problems with adverse reactions, tolerance, or limited effectiveness. Repetitive transcranial magnetic stimulation (rTMS), as a non-invasive neuroregulatory technique, offers a new treatment option for patients with PSD. This article reviews the application of rTMS in the treatment of PSD and its possible mechanism.

Objectives:To develop a machine learning prediction model for poor outcome of acute minor ischemic stroke (AMIS) at 90 days after onset and to explain the importance of various risk factors.Methods:Patients with AMIS admitted to the Second People's Hospital of Hefei from June 2022 to December 2023 were included retrospectively. AMIS was defined as the National Institutes of Health Stroke Scale (NIHSS) score ≤5 at admission. According to the modified Rankin Scale score at 90 days after onset, the patients were divided into a good outcome group (<2) and a poor outcome group (≥2). Recursive feature elimination (RFE) method was used to screen characteristic variables of poor outcome. Based on logistic regression (LR), supported vector machine (SVM), and extreme Gradient Boosting (XGBoost) machine learning algorithms, prediction models for poor outcome of AMIS were developed, and the predictive performance of the models was compared by the area under the curve (AUC) of receiver operating characteristic (ROC) curve and the calibration curve. Shapley Additive exPlanations (SHAP) algorithm was used to explain the role of characteristic variables in the optimal prediction model. Results:A total of 225 patients with AMIS were included, of which 152 (67.56%) had good outcome and 73 (32.44%) had poor outcome. Multivariate analysis showed that baseline NIHSS score, baseline systolic blood pressure, hypertension, diabetes, low-density lipoprotein cholesterol, homocysteine, body mass index, D-dimer, and age were the characteristic variables associated with poor outcome in patients with AMIS. The ROC curve analysis shows that the LR model had the best predictive performance (AUC=0.888, 95% confidence interval [ CI] 0.807-0.970), the next was the XGBoost model (AUC=0.888, 95% CI 0.796-0.980), while the SVM model had the lowest performance (AUC=0.849, 95% CI 0.754-0.944). The calibration curve showed that the LR model performed the best in terms of calibration accuracy. SHAP showed that baseline systolic blood pressure, baseline NIHSS score, diabetes, hypertension and body mass index were the top five risk factors for poor outcome of patients with AMIS. Conclusions:The LR algorithm has stable and superior performance in predicting poor outcome of patients with AMIS. Baseline systolic blood pressure, baseline NIHSS score, diabetes, hypertension and body mass index are the important risk factors for poor outcome of patients with AMIS.

More than 100 genes located on the X chromosome have been found to be associated with X-linked intellectual disability (XLID) to date, and NEXMIF is a pathogenic gene for XLID. In addition to intellectual disability, patients with NEXMIF gene mutation can also have other neurological symptoms, such as epilepsy, abnormal behavior, and hypotonia, as well as abnormalities of other systems. Two children with intellectual disability and epilepsy caused by NEXMIF gene mutation were treated in the Department of Pediatrics, Xiangya Hospital, Central South University from March 8, 2017 to June 20, 2020. Patient 1, a 7 years and 8 months old girl, visited our department because of the delayed psychomotor development. Physical examination revealed strabismus (right eye), hyperactivity, and loss of concentration. Intelligence test showed a developmental quotient of 43.6. Electroencephalogram showed abnormal discharge, and cranial imaging appeared normal. Whole exome sequencing revealed a de novo heterozygous mutation, c.2189delC (p.S730Lfs*17) in the NEXMIF gene (NM_001008537). During the follow-up period, the patient developed epileptic seizures, mainly manifested as generalized and absent seizures. She took the medicine of levetiracetam and lamotrigine, and the seizures were under control. Patient 2, a 6-months old boy, visited our department due to developmental regression and seizures. He showed poor reactions to light and sound, and was not able to raise head without aid. Hypotonia was also noticed. The electroencephalogram showed intermittent hyperarrhythmia, and spasms were monitored. He was given topiramate and adrenocorticotrophic hormone (ACTH). Whole exome sequencing detected a de novo c.592C>T (Q198X) mutation in NEXMIF gene. During the follow-up period, the seizures were reduced with vigabatrin. He had no obvious progress in the psychomotor development, and presented strabismus. There were 91 cases reported abroad, 1 case reported in China, and 2 patients were included in this study. A total of 85 variants in NEXMIF gene were found, involving 83 variants reported in PubMed and HGMD, and the 2 new variants presented in our patients. The patients with variants in NEXMIF gene all had mild to severe intellectual disability. Behavioral abnormalities, epilepsy, hypotonia, and other neurological symptoms are frequently presented. The phenotype of male partially overlaps with that of female. Male patients often have more severe intellectual disability, impaired language, and autistic features, while female patients often have refractory epilepsy. Most of the variants reported so far were loss-of-function resulted in the reduced protein expression of NEXMIF. The degree of NEXMIF loss appears to correlate with the severity of the phenotype.
Child ; Epilepsy/genetics* ; Female ; Humans ; Intellectual Disability/genetics* ; Male ; Muscle Hypotonia/complications* ; Mutation ; Phenotype ; Seizures/genetics* ; Strabismus/complications*

Objective: To summarize the clinical manifestations and gene variations of combined immunodeficiency caused by ORAI1 variation with a case report and literature review. Methods: The clinical data of the patient who was diagnosed with ORAI1 variation caused combined immunodeficiency in the Department of Pediatrics in Xiangya Hospital of Central South University in February 2018 were extracted and analyzed. The literature till August 2018 was searched with key words of 'ORAI1', and 'immunodeficiency' in both English and Chinese in the database of China national knowledge infrast ructure (CNKI), Wanfang and Pubmed. Results: The patient was a 15 months old girl with acute onset of bilateral ptosis after upper respiratory tract infection, which was rapidly progressed to systemic myasthenia and accompanied with recurrent respiratory tract infection during the treatment. The patient poorly to responded immunomodulatory therapy and anti-infection therapy. Laboratory tests demonstrated decreased complement C3 and NK cell (CD3^-CD56⁺), increased anti-thyroglobulin, thyroid peroxidase antibody and B lymphocyte (CD3^-CD19⁺), and slightly increased anti-acetylcholine receptor antibody. Genetic analysis showed the homozygous variation of ORAI1 gene exon l c.12 G>T (p.E4D), with heterozygostty of both parents. There were only 4 papers reporting this disease in the literature review. A total of 7 patients with ORAI1 gene variation were reported, including 3 homozygous variations, 2 heterozygous variations and 2 complex heterozygous variations. The clinical manifestations included early onset recurrent infection, congenital hypotonia, elevated serum IgA and IgM, decreased NK cells, and family history of hereditary diseases. Four of the 7 reported cases died of pulmonary infection and sepsis, and the other 3 survived with low muscular tone and poor self-care ability. Conclusions The most common clinical manifestations of ORAI1 variation caused combined immunodeficiency are recurrent infection and congenital hypotonia. Myasthenia induced recurrent respiratory tract infection is an important factor of poor prognosis in severe patients. There is a lack of effective treatment for this disease, and the prognosis is poor.

To investigate the effects of ventricular shunt placement in children with post-infective hydrocephalus.
 Methods: A total of 24 cases of post-infectious hydrocephalus, who received ventricular shunt, were enrolled. Age, gender, disease progression, clinical manifestation, laboratory data, treatment, prognosis, complication, and sequela for each patient were retrospectively reviewed.
 Results: Of the 24 cases, 8 had a full recovery, 11 had slight sequela, 2 had severe sequela, 1 was in vegetative state, and 2 died because of bacterial meningitis and tubercular meningitis. Epilepsy, mental impairment, visual and hearing damage were the main sequelae.
 Conclusion: Ventricular shunt is the preferred treatment in children with post-infective hydrocephalus, which shows positive clinical efficacy and can improve the long-term prognosis of such patients.
Child ; Humans ; Hydrocephalus ; Retrospective Studies ; Treatment Outcome ; Tuberculosis, Meningeal ; Ventriculoperitoneal Shunt

Objective: To investigate the clinical features, diagnosis and treatment of febrile infection-related epilepsy syndrome (FIRES). Methods: The clinical data of 12 children with FIRES admitted to Xiangya Hospital of Central South University from 2015 to 2018 were retrospectively analyzed. The basic information, clinical manifestations, electroencephalogram, imaging examination, treatment and prognosis were analyzed. Results: Of the 12 patients, 7 were male and 5 were female. The age of onset was (7.0±3.7)years (1.3 year to 13 years). The average hospitalization time (34-86 days, median 52 days). Twelve patients were healthy before the disease, and had fever before convulsion. The interval between fever and seizure was (3.5±1.7)days (1-7 days). The status epilepticus and consciousness deficit were the main clinical manifestations. The electrogram of 8 patients showed status epilepticus when admitted. 12 patients had disturbance of consciousness; the acute episodes were focal seizures (100%, 12/12) and generalized tonic-clonic seizures (41.7%, 5/12). All patients used 3-5 antiepileptic drugs (median 4), all treated with hormones and gamma globulin. 4 patients with ketogenic diet (KD) were treated within 2 weeks of onset, and the average duration from onset to electroencephalogram (EEG) improvement was (19.2±5.0)days. In 8 patients who did not use KD within 2 weeks of onset, the average duration from onset to EEG improvement was (29.9±9.6)days. Conclusions FIRES is more common in normal children with school age. The main manifestation is refractory status epilepticus in the days after acute fever, focal episodes of seizures, anti-epileptic drug resistance. Early initiation of KD produces a favorable prognosis.

Autoimmune encephalitis(AE) is one of the most rapidly developing research fields in pediatric neurology.Previous studies have indicated that delayed-use or non-use of immunotherapy will lead to poor prognosis.Therefore, this article summarizes the current opinion of immunotherapy and prognostic factors for AE in order to provide treatment guidance for clinicians.